Colorectal cancer is a leading cause of cancer-related death in the United States. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources to develop ideal chemoprevention remains an essential step in advancing the treatment of colorectal cancer. The candidate, Dr. Chong-Zhi Wang, is an experienced phytochemical scientist at University of Chicago. This application describes a development award for Dr. Wang, to successfully achieve his long-term career goals of obtaining the skills necessary to become an independent investigator in biomedical research, concentrating on the efficacy and mechanism of bioactive botanical extracts/compounds for treating colorectal cancer. Training for Dr. Wang will focus on advancing his knowledge of pharmacognosy and metabolism of phytoconstituents, understanding cancer pathophysiology, becoming proficient in biostatistics knowledge, and improving his grant writing ability. The advisory team is composed of senior experts from the University of Chicago and University of Illinois at Chicago. The Primary Mentor Dr. Chun-Su Yuan, a Principal Investigator of NIH Center for Botanical Research on Colorectal Cancer at University of Chicago, will closely direct Dr. Wang's training and research. Preliminary data showed that the different fractions from Scutellaria baicalensis extract (SbE) had opposing effects on human colorectal cancer cells. The hypothesis of this study is that if the baicalin and scutellarein, hydrophilic constituents, are removed from S. baicalensis extract or transformed into lipophilic constituents, the anticancer effects of the extract will increase significantly. The purpose of the research is to develop a new process for preparing an aglycon-rich fraction (ARF) of S. baicalensis extract in improving its anticancer activities and to elucidate the underlying mechanisms. The specific aims are as follows: Aim 1. Authentication, extraction and isolation of SbE and preparation of ARF. Aim 2. Evaluation of the effects of SbE and ARF on colorectal cancer and related mechanisms of action. Aim 3. Further investigation of ARF-induced apoptotic pathways. Data from this proposed study will have the potential to advance cancer treatment regimens, and improve the quality of life for patients suffering from colorectal cancer. Upon successful completion of this award, Dr. Wang will be fully prepared for his independent investigation of additional pharmacologically based studies using phytoconstituents against colorectal cancer. PUBLIC HEALTH RELEVANCE: Colorectal cancer is a leading cause of cancer related death in the United States. While advances have been made in developing effective treatment strategies for this cancer, chemotherapies are still limited by severe adverse effects and dose-limiting toxicity. This Project will use Scutellaria baicalensis, a Chinese herb medicine, with a new extract process to produce an active fraction, and evaluate the active fraction's anticancer effects on colorectal cancer.